Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: A GISAID exploratory analysis

Abstract

Massive usage of antiviral compounds during a pandemic creates an ideal ground for emergence of resistant strains. Remdesivir, a broad-spectrum inhibitor of the viral RNA-dependent RNA polymerase (RdRp), was extensively prescribed under emergency use authorization during the first 18 months of the COVID19 pandemic, before randomized controlled trials showed poor efficacy in hospitalized patients. RdRp mutations conferring resistance to remdesivir are well known from in vitro studies, and the huge SARS-CoV-2 sequencing effort during the ongoing COVID19 pandemic represents an unprecedented opportunity to assess emergence and fitness of antiviral resistance in vivo. We mined the GISAID database to extrapolate the frequency of remdesivir escape mutations. Our analysis reveals very low levels of remdesivir resistance worldwide despite massive usage.

Keywords: COVID-19; E802D; Molnupiravir; Nsp12; RNA-Dependent RNA polymerase; Remdesivir; Resistance; SARS-CoV-2.